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Phase I/II Study of Gefitinib and Concomitant Preoperative Radiotherapy in Patients with Locally Advanced Rectal Cancer

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Journal of Cancer Therapy 2012年第6期3卷 970-976页

作者： Abdelkarim SAllal Arnaud DRoth alessandra franzetti-pellanda Marta Bonet Pascal Gervaz Sabine Bieri Department of Radiation Oncology HFR-Hopital Cantonal de FribourgFribourgSwitzerland Department of Radiation Oncology University Hospital of GenevaGenevaSwitzerland Department of Surgery University Hospital of GenevaGenevaSwitzerland Oncologic Institute of Southern Switzerland Hospital San GiovanniBellinzonaSwitzerland Radiation Oncology Center Con-sorci Sanitari de TerrassaInstitut Oncologic del Valles(CST-HGC-CSPT)Terrassa-BarcelonaSpain Radiation Oncology Center Hospital of SionSionSwitzerland Radioonkologie Amsler AG LiestalSwitzerland.

Objective: To determine the recommended dose (RD) of gefitinib when combined with concomitant radiotherapy (RT) in a preoperative setting in patients with locally advanced rectal cancer. Secondary objectives were to evaluate acute toxicities, pathological response rate, progression-free and overall survival (OS). Materials and Methods: 20 patients with cT3-4 or cN+ cM0 tumors were enrolled. The planned RT consisted in 50 Gy given in 2 daily fractions of 1.25 Gy in 4 weeks. During RT, gefitinib was planned to be given orally once daily with 2 successive dose levels: 250 mg and 500 mg. Rectal surgery was scheduled 5 - 6 weeks after completion of RT. The median follow-up for all patients was 57 months. Results: Among the first cohort of 6 patients, 1 patient presented a dose limiting toxicity (DLT) (Grade 3 diarrhea/dehydration). In the second cohort, 2/6 patients presented with the same DLT so that 250 mg was considered as the RD. Main acute toxicities consisted in diarrhea (grade 2 - 3, 63%), and skin reaction (in RT fields grade 2 - 3 in 42%). The 5-year actuarial OS and loco-regional control rates were of 80% and 84% respectively. Conclusion: The concomitant daily administration of 250 mg of gefitinib with 50 Gy preoperative RT is feasible with manageable toxicity. The major pathologic response rate is encouraging, though it needs further confirmation. Distant metastasis still represents a concern and new strategies to overcome this issue are warranted.

关键词： Rectal Cancers Radiotherapy Gefitinib Acute Toxicity

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Outcome and prognostic factors in 110 consecutive patients with primary uterine leiomyosarcoma:A Rare Cancer Network study

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Chinese Journal of Cancer Research 2017年第6期29卷 521-532页

作者： alessandra franzetti pellanda Berardino De Bari Elisabeth Deniaud-Alexandre MarcoKrengli Paul Van Houtte Antonella Riehetti Salvador Villa Hadassah Goldberg EwaSzutowiez-Zielifiska Michel Bolla Heidi Rutten Marc Van Eijkeren Philip Poortmans Guido Henke Yavuz Anaeak Steve Chan Christine Landmann Carine Kirkove LueianoScandolaro Jacques Bernier Rene-Olivier Mirimanof Mahmut Ozsahin Centre Hospitalier Universitaire Vaudois(CHUV) 1011 LausanneSwitzerland Clinica Luganese Moncucco 6903 LuganoSwitzerland Centre Hospitalier R6gional Universitaire"Jean Minjoz" INSERMUMR109825030 BesangonFrance Hopital Tenon 75970 ParisFrance Centre Hospitalier Departemental 85925 VendeeFrance degli Studi del Piemonte Orientale e Ospedale Maggiore della Carifi 28100 NovaraItaly University Institut Jules Bordet 1000 BrusselsBelgium 8Ospedale di Circolo 21100 VareseItaly Ospedale di Circolo 21100 VareseItalyt Istituto Oncologico della Svizzera Italiana EOC6500 BellinzonaSwitzerland Catalan Institute of Oncology Universitat Autbnoma de Barcelona08916 Barcelona 08916Spain Rambam Medical Center 31096 HaifaIsrael Medical University 80210 GdanskPoland Hopital Michallon BP21738043Grenoble cedex 09France Radboud University Medical Center 6525 NijmegenThe Netherlands Ghent University Hospital 9000 GentBelgium Institute Verbeeten 90120 TilburgThe Netherlands Kantonsspital St.Gallen 9007St.GallenSwitzerland Karadeniz Technical University 61080 TrabzonTurkey Nottingham University Hospital NHS trustNG5 1PB NottinghamUnited Kingdom Kantonsspital Basel 4031 BaselSwitzerland UCL St.Luc 1200 BrusselsBelgium presidio Ospedaliero Sant'Anna 22100 ComoItaly Ospedale San Giovanni 6500 BellinzonaSwitzerland Clinique de Genolier Genolier1272 Switzerland Department of Radiation Oncology Centre Hospitalier Universitaire Vaudois(CHUV)University of LausanneSwitzerland

Objective： Primary uterine leiomyosarcomas （ULMS） are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. Methods： We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network （RCN）. Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics （FIGO） stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control （LC） and locoregional control （LRC）, overall survival （OS） and disease-free survival （DFS） rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. Results： All patients underwent surgery. Seventy-five patients （68%） received adjuvant radiotherapy （RT）, including brachytherapy in 18 （I 6%）. Seventeen patients （15 %） received adjuvant chemotherapy. Median follow-up was 58 （range, 6-240） months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. Conclusions： In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim p

关键词： Uterine leiomyosarcoma prognostic factors radiotherapy overall survival local control

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Genotoxicity testing for radon exposure： Dolichopoda （Orthoptera, Rhaphidophoridae） as potential bio-indicator of confined environments

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Current Zoology 2014年第2期60卷 299-307页

作者： Bianca GUSTAVINO Roberta MESCHINI Giulia franzetti Paolo GRATTON Giuliana ALLEGRUCCI Valerio SBORDONI Department of Biology University of Rome Tor Vergata Via della Ricerca Scientifica 1 00133 Rome Italy Department of Ecological and Biological Sciences Via San Camillo De Lellis snc University of Tuscia 011 O0 Viterbo Italy

Radon represents the major source of natural radioactivity in confined environments. Despite the clear evidence of a direct association between residential exposure and human lung cancer provided by case-control studies, results relating indoor exposure and genotoxic/mutagenic effect induction are still contradictory. The present study attempts to estimate the genotoxic effects induced by exposure to radioactive radon in wild cricket populations sampled from caves where varying concentrations of radon are present. Cave crickets are also tested as possible bio-indicator organisms of genotoxic potential of contaminated residential and confined environments. Six caves in Central Italy are considered covering a broad spectrum of radon radioactivity concentration （221-26,000 Bq/m3）. Dolichopoda specimens were sampled from each cave; both haemocytes and brain cells taken from individuals were tested for responsiveness to DNA damage induced by radon through the Comet assay. Specimens from the least radioactive cave, housed in controlled conditions for 60 days before analysis, were used as control group. Statistically significant increase of DNA damage was found in all groups of individuals from each cave, for both cell types. Very low values of all Comet parameters were found in control group individuals, which gave indications of a good responsiveness of the organism to the variable environmental levels of radioactive contamination. Results indicate that cave crickets represent a reliable tool for the detection of genotoxic potential induced by radioactive contamination of confined environments and can be proposed as a possible bio-indicator system for air （-radioactive） pollution related to indoor exposure [Current Zoology 60 （2）： 299-307, 2014].

关键词： High-LET natural-radioactivity Indoor exposure Cave crickets DNA primary damage Comet assay

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Autophagy precedes apoptosis during the remodeling of silkworm larval midgut

Autophagy precedes apoptosis during the remodeling of silkwo...

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广东省遗传学会第九届代表大会暨学术研讨会

作者： Eleonora franzetti 黄志君 Yan-Xia Shi Kun Xie Xiao-Juan Deng Jian-Ping Li Qing-Rong Li Wan-Ying Yang Wen-Nian Zeng Morena Casartelli Hui-Min Deng Silvia Cappellozza Annalisa Grimaldi Qingyou Xia 冯启理曹阳 Gianluca Tettamanti Department of Biotechnology and Life Sciences University of Insubria Laboratory of Insect Molecular Biology and Biotechnology Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular BreedingCollege of Animal ScienceSouth China Agricultural University Department of Biology Universita" degli Studi di Milano Guangdong Provincial Key Lab of Biotechnology for Plant Development School of Life SciencesSouth China Normal University

Although several features of apoptosis and autophagy have been reported in the larval organs of Lepidoptera during metamorphosis,solid experimental evidence for autophagy is still ***,the role of the two processes and the nature of their relationship are still *** this study,we perform a cellular,biochemical and molecular analysis of the degeneration process that occurs in the larval midgut of Bombyx mori during larval-adult transformation,with the aim to analyze autophagy and apoptosis in cells that die under physiological *** demonstrate that larval midgut degradation is due to the concerted action of the two mechanisms,which occur at different times and have different *** is activated from the wandering stage and reaches a high level of activity during the spinning and prepupal stages,as demonstrated by specific autophagic *** data show that the process of autophagy can recycle molecules from the degenerating cells and supply nutrients to the animal during the non-feeding *** intervenes *** fact,although genes encoding caspases are transcribed at the end of the larval period,the activity of these proteases is not appreciable until the second day of spinning and apoptotic features are observable from prepupal *** abundance of apoptotic features during the pupal phase,when the majority of the cells die,indicates that apoptosis is actually responsible for cell death and for the disappearance of larval midgut cells.

关键词： Apoptosis Autophagy Bombyx mori Insects Metamorphosis Midgut

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